AbstractIncarcerated persons have high rates of infectious diseases. Few data on the prevalence of sexually transmitted diseases in prisoners are available. This multi‐center cross‐sectional study enrolled 973 inmates from eight Italian prisons. Demographic and behavioral data were collected using an anonymous standardized questionnaire and antibodies to HIV, HCV, HBV, HSV‐2, and HHV‐8 were detected in a blood sample obtained from each person at the time of the enrollment in the study. Two hundred and two out of the 973 subjects (20.7%) had antibodies against HHV‐8. HHV‐8‐seropositive subjects were more likely to be older than 30 years with a higher educational level. HHV‐8 infection was associated significantly with HBV (P < 0.001) and HSV‐2 (P = 0.004) seropositivity and with previous imprisonments. Multivariate analysis showed that HHV‐8 infection in Italian inmates was associated with HBV (P < 0.001) and HSV‐2 (P = 0.002) seropositivity otherwise among foreigners inmates HHV‐8 was significantly associated with HBV infection (P = 0.05). One hundred and eighty‐six (21.2%) prisoners had anti‐HSV‐2 antibodies. At multivariate analysis HSV‐2‐positivity was significantly associated with HIV (P < 0.001) and HHV‐8 infections (P = 0.003), whereas it was inversely associated with HCV infection (0.004). A relatively high seroprevalence of HHV‐8 and HSV‐2 among Italian prison inmates was found. The association of HHV‐8 and HSV‐2 infections suggest sexual transmission of these viruses among Italian prison inmates. J. Med. Virol. 79:167–173, 2007. © 2006 Wiley‐Liss, Inc.